The effect of denosumab on disseminated tumor cells (DTCs) of breast cancer patients with neoadjuvant treatment: a GeparX translational substudy.

Pauline Wimberger, Jens-Uwe Blohmer, Petra Krabisch, Theresa Link, Marianne Just, Bruno Valentin Sinn, Eike Simon, Christine Solbach, Tanja Fehm, Carsten Denkert, Cristin Kühn, Kerstin Rhiem, Hans Tesch, Sherko Kümmel, Andrea Petzold, Oliver Stötzer, Cornelia Meisel, Jan Dominik Kuhlmann, Valentina Nekljudova, Sibylle Loibl
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Abstract

Background: Disseminated tumor cells (DTCs) in the bone marrow are observed in about 40% at primary diagnosis of breast cancer and predict poor survival. While anti-resorptive therapy with bisphosphonates was shown to eradicate minimal residue disease in the bone marrow, the effect of denosumab on DTCs, particularly in the neoadjuvant setting, is largely unknown. The recent GeparX clinical trial reported that denosumab, applied as an add-on treatment to nab-paclitaxel based neoadjuvant chemotherapy (NACT), did not improve the patient's pathologic complete response (pCR) rate. Herein, we analyzed the predictive value of DTCs for the response to NACT and interrogated whether neoadjuvant denosumab treatment may eradicate DTCs in the bone marrow.

Methods: A total of 167 patients from the GeparX trial were analyzed for DTCs at baseline by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Initially DTC-positive patients were re-analyzed for DTCs after NACT ± denosumab.

Results: At baseline, DTCs were observed in 43/167 patients (25.7%) in the total cohort, however their presence did not predict response to nab-paclitaxel based NACT (pCR rates: 37.1% in DTC-negative vs. 32.6% DTC-positive; p = 0.713). Regarding breast cancer subtypes, the presence of DTCs at baseline was numerically associated with response to NACT in TNBC patients (pCR rates: 40.0% in DTC-positive vs. 66.7% in DTC-negative patients; p = 0.16). Overall, denosumab treatment did not significantly increase the given DTC-eradication rate of NACT (NACT: 69.6% DTC-eradication vs. NACT + denosumab: 77.8% DTC-eradication; p = 0.726). In TNBC patients with pCR, a numerical but statistically non-significant increase of DTC-eradication after NACT + denosumab was observed (NACT: 75% DTC-eradication vs. NACT + denosumab: 100% DTC-eradication; p = 1.00).

Conclusion: This is the first study worldwide, demonstrating that neoadjuvant add-on denosumab over a short-term period of 24 months does not increase the DTC-eradication rate in breast cancer patients treated with NACT.

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denosumab对新辅助治疗乳腺癌患者弥散性肿瘤细胞(dtc)的影响:一项GeparX翻译亚研究
背景:原发性乳腺癌患者骨髓中弥散性肿瘤细胞(dtc)约占40%,预后较差。虽然双膦酸盐抗再吸收治疗被证明可以根除骨髓中的微小残留疾病,但denosumab对dtc的影响,特别是在新辅助治疗中,很大程度上是未知的。最近的GeparX临床试验报道,作为nab-紫杉醇为基础的新辅助化疗(NACT)的附加治疗,denosumab并没有提高患者的病理完全缓解(pCR)率。在此,我们分析了dtc对NACT反应的预测价值,并询问新辅助denosumab治疗是否可以根除骨髓中的dtc。方法:使用泛细胞角蛋白抗体A45-B/B3,通过免疫细胞化学分析167例来自GeparX试验的患者基线dtc。最初dtc阳性患者在NACT±denosumab后再次分析dtc。结果:在基线时,在整个队列中有43/167例患者(25.7%)观察到dtc,但它们的存在并不能预测基于nab-紫杉醇的NACT的反应(pCR率:dtc阴性37.1%对dtc阳性32.6%;p = 0.713)。对于乳腺癌亚型,基线时dtc的存在与TNBC患者对NACT的反应有数值相关性(pCR率:dtc阳性患者为40.0%,dtc阴性患者为66.7%;p = 0.16)。总体而言,denosumab治疗并没有显著提高NACT的给定dtc根除率(NACT: 69.6% dtc根除vs. NACT + denosumab: 77.8% dtc根除;p = 0.726)。在采用pCR的TNBC患者中,观察到NACT + denosumab后dtc根除数量增加,但统计学上不显著(NACT: 75% dtc根除vs. NACT + denosumab: 100% dtc根除;p = 1.00)。结论:这是全球首个研究表明,在短期24个月的时间内,新辅助治疗的denosumab不会增加NACT治疗的乳腺癌患者的dtc根除率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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